Skeletal Muscle Plasticity As An Indicator of Functional Performance Post-Stroke

描述(由申请人提供)： 与中风后偏瘫相关的一个主要损害是未能在有目的的复杂协同作用(例如，行走时的协调)下对肌肉力量(即肌肉力量)进行快速分级调整。毫不奇怪，中风对走路的影响是 重要的是，只有不到50%的幸存者进展到独立的社区走动。即使在那些能够独立行走的人中，显著的残留缺陷仍然存在，平衡和步态速度仍然存在，大约75%的中风后患者报告与步行有关的活动受限。在生活在美国的近600万中风幸存者中，肌肉无力是最突出的运动后果，也是这一大型临床队列中最能预测功能性残疾的指标。到目前为止，偏瘫患者肌肉功能障碍的生理机制在很大程度上还没有被研究。此外，关于旨在减轻中风后人群肌肉功能受损的干预措施的有效性和随之而来的功能后果的证据是模棱两可的，修复偏瘫肌肉无力的可行治疗方案仍然是生物医学研究最紧迫的挑战之一。我们认为，肌肉力量(肌肉力量和速度的产物)的产生受损是中风后功能性(行走)残疾的原因。此外，协调缺陷也是功能表现的关键决定因素。我们已经开发了一个全面的理论框架，它定义和测量了肌肉功能和协调性障碍的潜在因素，并将把这个框架应用于中风后使用爆炸阻力(力量)训练的步行优化。我们在四年的资助期内的目标是：1)量化导致中风后受损肌肉发电的神经和肌肉适应；2)评估力量训练对瘫痪和非瘫痪肌肉神经和肌肉适应的影响；3)确定力量训练和运动改善后神经和肌肉适应变化之间的关系。拟议工作的创新方面包括新的培训干预；先进的磁共振评估；以及我们提议的协调的独特措施。我们认为：a)中风后的神经和肌肉适应与肌肉发电和运动能力受损有关，b)力量训练通过解决潜在的神经和肌肉元素来减轻功能缺陷，c)训练后的功能改善是基于改善对肌肉发电最重要的神经和肌肉贡献因素。如果正确，所产生的数据将提供一个全新水平的证据，证明这种新的干预策略在改善功能表现方面的有效性，以及周围肌肉特性作为中风后运动能力预测指标的重要性。

DESCRIPTION (provided by applicant): A primary impairment associated with post-stroke hemiparesis is the failure to make rapid graded adjustment of muscle force (i.e. muscle power) within the context of purposeful complex synergies (e.g., coordination during walking). Not surprisingly, the impact of stroke on walking is significant, with less than 50% of survivors progressing to independent community ambulation. Even among those who achieve independent ambulation, significant residual deficits persist in balance and gait speed, with ~75% of persons post-stroke reporting limitations in mobility related to walking. Muscle weakness is the most prominent motor consequence among the nearly 6 million survivors of stroke living in the United States and the strongest predictor of functional disability in this large clinical cohort. To date, the physiological mechanisms that contribute to muscle dysfunction in hemiparetic subjects are largely unstudied. Moreover, evidence regarding the efficacy of interventions aimed at attenuating impaired muscle function and the ensuing functional consequences in the post-stroke population is equivocal and viable therapeutic options to remediate hemiparetic muscle weakness remain among the most pressing challenges for biomedical research. We propose that impaired muscle power (the product of muscle strength and velocity) generation is causal of functional (walking) disability post-stroke. In addition, coordination deficits are also critical determinants of functional performance. We have developed a comprehensive theoretical framework that defines and measures the factors underlying disordered muscle function and coordination and will apply this framework to Post-stroke Optimization of Walking using Explosive Resistance (POWER) training. Our goals over the four year funding period are to 1) quantify neural and muscular adaptations that contribute to impaired muscle power generation post-stroke; 2) assess effects of POWER training on neural and muscular adaptations in paretic and non-paretic muscle; and 3) determine the relationship between changes in neural and muscular adaptations following POWER training and locomotor improvements. Innovative aspects of the proposed work include the novel training intervention; the advanced magnetic resonance assessments; as well as the unique measure of the coordination that we propose. It is our belief that: a) neural and muscular adaptations following stroke are associated with impaired muscle power generation as well as locomotor ability, b) POWER training attenuates functional deficits by addressing the underlying neural and muscular elements and c) functional improvements following training are predicated on improving the most prominent neural and muscular contributors to muscle power generation. If correct, the data generated will provide an entirely new level of evidence regarding the effectiveness of this novel intervention strategy on improving functional performance as well as the importance of peripheral muscle properties as predictors of locomotor ability post-stroke.